The objectives of this research project involve the search for biologically active constituents in the plant family Compositae. The work is particularly oriented toward the isolation and structure elucidation of cytotoxic and anti-neoplastic sesquiterpene lactones and acetylenic natural products from the subtribe Melampodiinae. Genera of this subtribe presently under investigation are: Melampodium, Clibadium, Desmanthodium, Polymnia, Calea and Tetragonatheca. Nearly 30 new sesquiterpene lactones have been isolated from the above genera, mainly from Melampodium. Presently separations of sesquiterpene lactones from active fractions of M. cinereum (NSC B 9000555 and B 900556) are in progress. Major attention in our research is directed toward the structure-activity relationships in the natural and synthetically modified plant constituents, since antineoplastic activity of sesquiterpene lactones seems to depend not only on the presence of certain functional groups (alpha-methylene-gamma-lactones) but more importantly on the actual shape as well as the lipophilicity of these active principles.